For effective treatment and diagnosis of disease, it is advantageous to be able to image affected organs. There are many widely used types of imaging; however, these techniques do not have the versatility or contrast to look at the vasculature or the lymphatic system. An emerging technology to study these systems is an optical imaging technique referred to as near-infrared fluorescence (NIRF) imaging (˜700-900 nm), which has excellent safety because it does not involve ionizing radiation, has minimal interference from blood and tissue autofluorescence (˜500-600 nm) (i.e., background signal/fluorescence), and is non-invasive. The fluorescence imaging method involves irradiating fluorescent dye with light and detecting fluorescence emitted from the dye, and is widely used in various types of biological imaging. This method is used in angiography and can be used for intraoperative assessment of vessel function and/or metastasis. Unlike other techniques, NIRF imaging also has the capability to image lymphatic systems, giving important information to clinicians about lymphatic architecture and function in a patient. Nevertheless, NIRF imaging faces challenges due to its inability to image deep tissue (can only image ˜1 cm into the body because of light scattering).
ICG is a clinically used dye in NIRF imaging (with an 820 nm emission) and is the only NIRF molecule approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) for human use. ICG is indicated for determining cardiac output, hepatic function and liver blood flow, and for ophthalmic angiography. ICG is used off-label or in research to visualize fluid-filled anatomical structures (for example, blood, cerebrospinal fluid, lymph, or urine) or as a contrast agent for vascular, renal, or excretory pathways (1). In aqueous environments, ICG molecules aggregate and ICG fluorescence readily degrades (reducing the overall fluorescence intensity) (2-5). In blood, ICG binds to plasma proteins, partially and temporary improving its fluorescence intensity, but eventually dissociates and becomes subjected to degradation in aqueous fluid. In vivo ICG fluorescence intensity and duration may vary with fluctuating plasma protein and lipoprotein concentrations and interindividual variation.
Recent reports on ICG and liposomes with diverse physiochemical characteristics describe resource-intensive preparation procedures (≥4 steps) to encapsulate ICG in liposomes (8-12). However, these liposomes with varying compositions were prepared without a full understanding of the interactions between ICG and lipids. Under certain conditions, when ICG is encapsulated in the aqueous compartment of liposomes it can by default partially and physically interact with phospholipids in the liposome membrane. The lipid-ICG binding under these methods and compositions involves incomplete and unstable interactions. These formulations are not intended to intercalate or embed ICG in lipids. The results vary in the stability and quantum yield of ICG as well as in its use as an imaging product. Also, only a fraction of ICG may be encapsulated in the aqueous compartment of liposomes, thus requiring removal of the free ICG from the preparation procedure—a step that increases the potential of contamination and adds cost due to wastage and separation procedures.
There is need for improved ICG delivery systems.